Both the humoral and cellular arms of the immune response contribute to control of virus infections. Ectromelia, an orthopox virus infection of mice has been selected as a model system for studying host-virus interactions. It was found that Ly-2+ T cells are sufficient for in vivo resistance to this virus and that in vitro secondary responses to vaccinia are effected by interactions between Ly-2+ helper and effector cells. Interleukin-2 appears to mediate the interactions between these subsets of T cells.